Risankizumab as a Therapeutic Approach for Recalcitrant Pyoderma Gangrenosum.

ABSTRACT: Pyoderma gangrenosum (PG) is a neutrophilic dermatosis that is challenging to diagnose and treat. Clinicians frequently use fast-acting corticosteroids, which are subsequently combined with slower-acting immunosuppressants to progressively taper the corticosteroid dosage. Current research is focused on the use of monoclonal antibodies (mAbs) directed against target molecules involved in the pathogenesis of PG. However, available data on their efficacy are based on sporadic case reports and clinical experiences, so the authors aimed to evaluate the efficacy of risankizumab, an anti-interleukin-23 mAb, in the management of two complex PG cases. The authors enrolled two patients with PG who were already treated with immunosuppressive therapies. Their management was based on the off-label use of an mAb directed against the p19 subunit of interleukin-23: risankizumab. Patients received subcutaneous injections of 150 mg at the start of treatment, at week 4, and then every 10 weeks thereafter. Systemic therapy was combined with local management of ulcers, based on the principles of TIME (tissue, infection, moisture balance, and epithelialization) applied to the inflammatory and noninflammatory phases of PG. Clinical resolution was obtained at week 24 for patient 1 and week 16 for patient 2 and was maintained until week 40, without adverse effects or disease recurrence. These clinical cases demonstrate that risankizumab is a valid tool in terms of efficacy and safety for complicated cases of multirefractory PG when provided in parallel with local personalized wound management.

Fluorescence-Based Evaluation of Bacterial Load in Perilesional Skin: A Comparison Between Short Stretch Bandage and Zinc Oxide Bandage.

Bacterial proliferation plays a well-known role in delayed tissue healing. To date, the presence of microorganisms on the wound bed can be detected by skin swabs or skin biopsies. A novel noninvasive fluorescence imaging device has recently allowed real-time detection of bacteria in different types of wounds through endogenous autofluorescence. The fluorescence signals detected by the device provide health workers with a visual indication of the presence, load, and distribution of bacteria. The aim of our study was to evaluate the level of bacterial colonization in perilesional skin of patients affected by venous leg ulcers treated with 2 different types of bandages: short stretch bandage and zinc oxide bandage. We conducted a monocentric prospective study, enrolling 30 patients with venous leg ulcers, divided into 2 groups: group A was treated with short stretch bandage and group B with zinc oxide bandage. A complete patient's assessment was performed once a week for 3 weeks. Levels of potentially harmful bacteria in perilesional skin were detected using a fluorescent device by 2 experienced operators on the frames taken at individual injuries, while pain was evaluated with the Numerical Rating Scale. After 3 weeks, we observed a reduction in the bacterial colonization levels of the perilesional skin by 68.67% for group A and 85.54% for group B. All the patients had a statistically significant reduction in bacterial load (P < .001), and a statistically significant difference was identified between the 2 groups (P = .043). No statistically significant differences were found between the 2 groups in terms of pain relief (P = .114). Our study demonstrated that the application of zinc oxide bandage provides a higher reduction in bacterial load perilesional skin. On the other hand, we found no difference between the 2 bandages in terms of pain symptom reduction.

Ultra-High Frequency UltraSound (UHFUS) Assessment of Barrier Function in Moderate-to-Severe Atopic Dermatitis during Dupilumab Treatment.

Atopic dermatitis (AD) is a chronic multifactorial inflammatory disease characterized by intense itching and inflammatory eczematous lesions. Biological disease-modifying drugs, such as dupilumab are recommended for patients with moderate-to-severe AD, refractory to systemic immunosuppressive therapies. Disease monitoring is performed by clinical scores. Since 1970, however, the use of ultrasound and particularly high-frequency ultrasound (HFUS), has identified alterations in dermal echogenicity, called the subepidermal low-echogenic band (SLEB), that correlates with disease severity and response to treatment. We enrolled 18 patients with moderate-to-severe AD, divided into two groups: twelve patients in the dupilumab treatment (Group A) and six patients in standard treatment, from February 2019 to November 2019. We performed ultra-high frequency ultrasound (UHFUS) evaluation of lesional and non-lesional skin, focusing on SLEB average thicknesses measurement, epidermal thickness, and vascular signal in correlation with objective disease scores (EASI, IGA), patient's reported scores (Sleep Quality NRS and Itch NRS), and TEWL and corneometry at baseline (T0), after 1 month (T1) and 2 months (T2). The SLEB average thickness measurement, vascular signal, and epidermal thickness showed a statistically significant reduction in lesional skin of the biological treatment group and no significant reduction in non-lesional skin in both groups. In the lesional skin of the standard treatment group, only epidermal thickness showed a statistically significant reduction. Our study demonstrates that SLEB measurement, vascular signals, and epidermal thickness could be used as objective parameters in monitoring the AD treatment response, while the presence of SLEB in non-lesional skin could be used as a marker of subclinical inflammation and could predict development of clinical lesions, suggesting a pro-active therapy. Further follow-up and research are needed to clarify the association of SLEB decrease/disappearance with a reduction of flares/prolongment of the disease remission time.

Ultra-High-Frequency Ultrasound as an Innovative Imaging Evaluation of Hyaluronic Acid Filler in Nasolabial Folds.

Dermal hyaluronic acid (HA) fillers are used for nasolabial fold correction, but no study is still available on the use of ultra-high-frequency ultrasound (UHFUS) with 70 MHz probes for the evaluation of HA distribution and wrinkle amelioration. We selected 13 patients who received HA filler, evaluated before (Time (T) 0) and after injection (T1), and after 24 weeks (T2). The dermal thickness and distribution of HA were registered, as well as the Wrinkle Severity Rating Scale (WSRS), Global Aesthetic Improvement Scale (GAIS), and wrinkle 3D fullness. The UHFUS dermal thickness was increased by 11% for both sides at T1 and by 7.4% and 6.8% for the right and left side, respectively, at T2 (p < 0.01). The 3D wrinkle fullness showed a T1 increase (+0.59 cc and +0.79 cc for the right and left side, respectively) with a T2 maintenance of 45% of the T1 fullness (p-value < 0.001). The only clinical score significantly modified was WSRS, with a reduction of 56% at T1 and of 47.1% at T2 (p-value < 0.001). Our study then demonstrated the efficacy of UHFUS in the assessment of nasolabial fold correction, representing also the first multi-modal evaluation of HA persistence and its visual subsequent aesthetic results.

Assessment and Monitoring of Nail Psoriasis with Ultra-High Frequency Ultrasound: Preliminary Results.

Psoriatic onychopathy is one of the clinical presentations of psoriasis and a well-known risk factor for the development of psoriatic arthritis. High-frequency ultrasounds (HFUS > 20 MHz) have recently been used to evaluate the nail apparatus of healthy and psoriatic subjects. The aim of our study was to detect by means of ultra-high-frequency ultrasound (UHFUS 70-100 MHz) alterations of the nail bed and matrix in patients with psoriatic onychopathy and to monitor these parameters during the treatment with monoclonal antibody (mAb). We enrolled 10 patients with psoriatic onychopathy and naive to previous biologic therapies. Patients were evaluated at baseline, after 1 month and after 3 months from the beginning of mAb therapy by a complete clinical assessment and US evaluation. A UHFUS examination with a 70 MHz probe was performed on the thumbnail (I), the index fingernail (II) and the nail with greater clinical impairment (W). The following measurements were analyzed: nail plate thickness (A), nail bed thickness (B), nail insertion length (C), nail matrix length (D) and nail matrix thickness (E). Among the various parameters analyzed, some measures showed a statistically significant decrease with p-value < 0.05 (t0 WA = 0.52 mm vs. t2 WA = 0.42 mm; t0 WB = 2.8 mm vs. t2 WB = 2.4 mm; t0 WE = 0.76 mm vs. t2 WE = 0.64 mm; t0 IIA = 0.49 mm vs. t2 IIA = 0.39 mm). In conclusion, UHFUS could represent a viable imaging technique for the real-time evaluation and monitoring of psoriatic onychopathy, thus supporting the clinical parameters and revealing any subclinical signs of early drug response.

Serum Amyloid A: A Potential New Marker of Severity in Hidradenitis Suppurativa.

Introduction: Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease with systemic inflammation and high impact on quality of life. Treatment strategies are still inadequate with a lack of inflammation biomarkers. We conducted a prospective study to assess the correlation between serum amyloid A (SAA) levels and active lesion count; disease severity; Dermatology Life Quality Index (DLQI); smoking; BMI; and lesion sites. Methods: Forty-one patients (M/F: 22/19) were enrolled. Demographic, clinical, laboratory, and therapeutic data were assessed at baseline on patients not under treatment or in wash-out from systemic treatment for at least 2 weeks. Associations were investigated by univariate and multivariate analyses. Results: SAA levels were significantly associated with number of nodules (p = 0.005), abscesses (p < 0.001), fistulas (p = 0.016), and severe IHS4 (p = 0.088 and r = 0.514). Gluteal localization was correlated with high values of mSartorius and severe IHS4. Conclusions: We recommend assessment of SAA levels to monitor therapeutic response in patient with HS in order to prevent disease's flare and potential complications.

Pyoderma gangrenosum in a patient with Dubowitz syndrome: a new comorbidity?

INTRODUCTION: Dubowitz syndrome is a rare genetic disease with only a few cases reported in the literature. It is characterized by growth retardation, microcephaly, facial dysmorphism and higher risk of developing cancer and cardiomyopathies. PG is an autoinflammatory disorder that causes painful ulcers to develop on the skin and has not been previously associated with Dubowitz syndrome. CASE PRESENTATION: The authors report the case of a 50-year-old female with Dubowitz syndrome who developed painful ulcerative lesions. An incisional biopsy was performed to rule out other diagnoses, and a subsequent clinical diagnosis of PG was made. The patient was treated with specialized wound dressings and oral glucocorticoids. The clinical picture improved consistently after 7 weeks of therapy. CONCLUSIONS: This case report, to the authors' knowledge, is the first to suggest a possible association between Dubowitz syndrome and PG and also to indicate an effective treatment.

An Integrated Systemic and Local Wound Management in Recalcitrant Pyoderma Gangrenosum.

Pyoderma gangrenosum (PG) is a neutrophilic inflammatory dermatosis, whose management still represents a clinical challenge due to frequent unresponsive cases. The aim of our study was to evaluate the efficacy of a novel, combined approach including local wound management, based on the principle of PG-TIME and a systemic therapy with an anti interleukin (IL)-17A monoclonal antibody (mAb). We presented a case of a 37-year-old female patient, affected by multi-refractory PG. The patient was treated with a combined approach of both local and systemic therapy. Wound clinical improvement was assessed by Wound Bed Score (WBS), wound size was evaluated through 3D camera laser scanner, and pain was evaluated with visual analog scale (VAS). After 52 weeks of therapy, the association of local wound management with ixekizumab 80 mg [160 mg at time (T) 0; 80 mg every 2 weeks until week 12; 80 mg every 4 weeks] allowed us to perform skin grafting and obtain complete wound healing. Our clinical case demonstrated the efficacy of a novel combination therapy for the treatment of recalcitrant PG based on IL-17 mAbs and local wound management built on the main features of PG-TIME.